The objectives of this proposal are to determine the safety and analgesic efficacy of transnasal ketamine in a Phase I clinical study as the first step towards FDA approval and commercialization. Preliminary human clinical evidence indicates that transnasal ketamine induces analgesia for a variety of conditions associated with malignant pain, including cancer breakthrough pain. Analgesia occurs within seconds following administration and appears to last for periods of up to 1 hour. Transnasal ketamine does not induce changes in blood pressure or heart rate and does not demonstrate evidence of toxicity to the nasal mucosa following repetitive administration. The proposed Phase I trial is designed as a randomized placebo-controlled double blind, cross-over study in patients with chronic malignant pain experiencing breakthrough pain. The management of breakthrough pain in many patients is not well controlled by the variety of analgesics currently on the market, the most common of which are immediate-release narcotics. These agents are typically slow in onset of action and cause side effects including nausea, vomiting, constipation, myoclonus, and sedation. Transnasal ketamine may offer a significant advantage in that it can be self-administered and has a rapid onset of action devoid of these side effects. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE